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Biomedical subjects

F Bressolle

Publications and source records attributed to F Bressolle.

At least 127 records · Page 7Linked to original sources
PubMed1992

Disposition of roxithromycin in the epididymis after repeated oral administration.

The epididymal penetration of roxithromycin was studied in order to evaluate the drug for use in the treatment of epididymo-orchitis. Seventeen patients hospitalized for surgery as part of treatment for prostatic adenoma or prostatic cancer were premedicated orally with roxithromycin 150 mg bd for three days followed by 150 mg pre-operatively (3 h before surgical incision). Roxithromycin concentrations in serum and epididymis were determined by microbiological assay. The mean epididymal concentrations were 6.48 +/- 4.88 and 5.98 +/- 3.92 mg/kg for left and right epididymis respectively and the corresponding mean tissue/serum ratios 0.88 +/- 0.57 and 0.84 +/- 0.53. The wide intersubject variation in the concentration of roxithromycin found in serum and tissue is commonly seen with other macrolide antibiotics. The concentrations observed in this study in serum and tissue were greater than the MIC90s for Chlamydia trachomatis (0.25 to 1 mg/L), and Ureaplasma urealyticum (0.5 mg/L).

Adenoma↗
PubMed1992

Endotracheal and aerosol administrations of ceftazidime in patients with nosocomial pneumonia: pharmacokinetics and absolute bioavailability.

Pharmacokinetic studies on ceftazidime, an aminothiazole cephalosporin with a wide spectrum of antibacterial activity, including activity against Pseudomonas aeruginosa, were performed in patients with nosocomial pneumonia. The concentration-time profiles of ceftazidime in plasma, urine, and bronchial secretions of 12 patients were investigated after intravenous (i.v.) (n = 12), endotracheal (n = 10), and aerosol (n = 5) administrations. In all cases a 1-g dose was administered. Concentrations of drug in all samples were assayed by high-performance liquid chromatography with UV detection. The elimination of the drug from the blood followed a biexponential (i.v. administration) or a monoexponential (endotracheal and aerosol administrations) decay, with an elimination half-life of 6 h and a total body clearance of 4.2 liters/h. The apparent volume of distribution was 0.36 liter/kg of body weight. Renal clearance of the drug accounted for 58% of the total clearance; 66% +/- 17.7%, 33.5% +/- 17.3%, and 6.59% +/- 3.45% of the administered dose were eliminated in urine as parent drug after i.v., endotracheal, and aerosol administrations, respectively. The absolute bioavailabilities were 0.47 and 0.08 for endotracheal and aerosol administrations, respectively. Very high concentrations were found in bronchial secretions after local administration. The MICs for 90% of the most important pathogens responsible for nosocomial infections were exceeded by concentrations in bronchial secretion for up to 12 h after i.v. infusion and for up to 24 h after endotracheal and aerosol administrations.

Adult↗
PubMed1991

Pharmacokinetics of sulpiride in humans after intravenous and intramuscular administrations.

The pharmacokinetics of sulpiride in plasma, red blood cells (RBC), and urine were investigated after administration of 100 mg by the iv route to 15 subjects and by the im route to 12 subjects. The concentrations of sulpiride in plasma, RBC, and urine were measured by HPLC. All the data were consistent with a two-compartment, open-body model. After iv administration, the mean +/- SD apparent elimination half-life of sulpiride was 6.47 +/- 1.00 h, and the mean +/- SD volume of distribution at steady state was 0.94 +/- 0.23 L/kg. Renal clearance (119.5 +/- 28.2 mL/min) was very close to total clearance (127.8 +/- 26.2 mL/min). In urine, the mean +/- SD recovery in form of the unchanged drug was 90.0 +/- 9.68% of the administered dose, and the excretion rate versus time showed an elimination half-life similar to that found in plasma. The values of all these parameters were very close to those obtained after im administration. The sulpiride partition coefficient between RBC and plasma did not show any significant change as a function of time and concentration, with a mean value +/- SD of 1.00 +/- 0.043, indicating that sulpiride is evenly distributed between RBC and plasma. The pharmacokinetic parameters determined from the plasma and the RBC data were similar.

Analysis of Variance↗
PubMed1991

Bayesian estimation of doxorubicin pharmacokinetic parameters.

Doxorubicin was given by brief i.v. infusion (doses ranging from 25 to 72 mg/m2) to 28 patients for 2-7 successive courses of chemotherapy (68 courses studied in all). A Bayesian approach was developed to determine the individual pharmacokinetic parameters of doxorubicin. Statistical characteristics of the population pharmacokinetic parameters were first evaluated for 19 patients and a total of 30 courses, which, when combined with 4 individual plasma concentrations of drug, led to a Bayesian estimation of individual pharmacokinetic parameters for the remaining 38 courses. The estimated parameters for the elimination phase (A3/V1 and t1/2 elimination) and the residual plasma level at 48 h as computed by Bayesian estimation on this reduced sub-optimal sampling protocol were compared with a maximal likelihood estimation of these parameters. No statistically significant differences were found. Performance of the developed methodology was evaluated by computing bias and precision. The mean errors were -0.0315 x 10(-4) l-1 for A3/V1, 0.0839 h for t1/2 elimination, and -0.22 ng/ml for c(48 h). The precision of the prediction of these three parameters (0.304 x 10(-5) l-1, 3.34 h, and 0.659 ng/ml, respectively) remained lower than the interindividual standard deviation (1.42 x 10(-4) l-1, 14.9 h, and 4.54 ng/ml, respectively). This procedure enables the estimation of individual pharmacokinetic parameters for doxorubicin at minimal cost and minimal disturbance of the patient.

Bayes Theorem↗
PubMed1991

Steady-state pharmacokinetics of ciprofloxacin in plasma from patients with nosocomial pneumonia: penetration of the bronchial mucosa.

A 30-min intravenous (i.v.) infusion of 200 mg of ciprofloxacin was administered twice daily to 12 patients with nosocomial pneumonia scheduled to undergo diagnostic fiberoptic bronchoscopy. The pharmacokinetics of ciprofloxacin were examined at the presumed steady state after 5 days of treatment. Eleven successive plasma samples were collected in the interval from 0 to 12 h after administration, and bronchial mucosa samples were taken 2 h after administration. Concentrations of drug in all samples were assayed by high-performance liquid chromatography with fluorimetric detection. The results showed that the kinetics in plasma did not differ from those determined previously in healthy volunteers. The mean concentrations in plasma peaked at 4.94 +/- 2.90 mg/liter at the end of infusion. The terminal half-life was 4.95 +/- 2.81 h, and the mean residence time 6.13 +/- 3.17 h. A large volume of distribution was calculated: 2.59 +/- 1.43 liters/kg. Mean total body clearance was 23.3 +/- 10.1 liters/h. The concentrations in bronchial mucosa reached 21.6 +/- 5.63 micrograms/g 2 h after drug intake. The tissue-versus-plasma concentration ratios ranged from 10.1 to 26.3 (mean value, 16.9 +/- 5.43). After 6 to 12 days of i.v. treatment, four patients were switched to oral ciprofloxacin. We propose a model for the simultaneous fit of the concentration-time curves obtained after i.v. infusion and oral dosing. The concentrations in tissue observed in this study were in excess of the MICs for bacteria considered to be susceptible to ciprofloxacin.

Administration, Oral↗
PubMed1991

Altered tobramycin pharmacokinetics during chemoprophylaxis in bladder surgery.

The effect of bladder surgery on the pharmacokinetics of tobramycin in hospitalized patients was studied. Fourteen patients with vesical neoplasia undergoing urinary tract surgery were given tobramycin in a dose of 2 mg/kg of body weight. Each patient received the dose at the induction of anesthesia, about 1 h before surgical incision. For seven patients, the drug was also administered 3 weeks later when nutritional conditions were normal. The pharmacokinetic parameters were determined by a two-compartment open model. Except for renal clearance, no significant difference appeared between pharmacokinetic parameters determined from serum data during peri- and postoperative periods. During this work, tobramycin excretion in urine was studied. Twenty-four hours after drug administration, the mean urine tobramycin levels were 25.5 +/- 9.06 and 41.6 +/- 21.5 micrograms/ml after peri- and postoperative administration, respectively; these values were higher than the MICs for most urinary tract pathogens. Seventy-two hours after perioperative administration, the mean value was still elevated (3.54 micrograms/ml), but 72 h after postoperative administration, the urinary tobramycin concentration was not detectable. The percentages of tobramycin recovered unchanged in urine were 54 and 79% after peri- and postoperative administration, respectively. When tobramycin was administered during surgery, a long terminal log-linear phase, with a mean half-life of 25.6 h, was detected. The ratio of renal clearance to total body clearance was 0.52 and 0.79 after peri- and postoperative administration, respectively.

Aged↗
PubMed1991

[Diffusion of norfloxacin in epididymal tissue].

Norfloxacin, a "second generation" compound of the quinolone group, was administered orally, before surgery, every 12 h during successive three-day periods at dose of 400 mg to ten patients hospitalized for prostatic adenoma or for prostatic cancer. On the day of surgery, a 400 mg-last dose was administered. Unchanged norfloxacin was assayed by high performance liquid chromatography with fluorescence detection. The Cmin value was 1.2 +/- 0.77 mg/l. Concurrent norfloxacin concentrations in plasma and epididymal tissue (left and right) were determined, about 4 h after the last drug intake, the epididymal level was 3.4 +/- 1.9 micrograms/g. This value was above the MIC90 for most sensitive organisms. The ratio (+/- SD) of drug concentration in epididymal tissue and in plasma was 3. 74 +/- 2.10 (range 1.66-10.2). The epididymal level of norfloxacin was strongly correlated with, area under curve (p less than 0.001) and plasma concentration (p less than 0.01).

Aged↗
PubMed1990

High-performance liquid chromatographic determination of 4-amino-5-chloro-N-[(1-ethylimidazolin-2-yl)methyl]-2-methoxybenzamide and its metabolite in biological fluids. Applications in pharmacokinetic studies.

A high-performance liquid chromatographic method with spectrofluorometric detection has been developed for the analysis of a new substituted benzamide and its metabolite in body fluids. The detection was performed at 270 nm for excitation, and 370 nm for emission. The proposed technique is selective, reliable, and sensitive. The detection limit is 1 ng/mL for the parent drug and 2 ng/mL for the imidazole derivative. The reproducibility of the analytical method through statistical coefficients is approximately 5%. The accuracy of the method is good; that is, the relative error is less than 2%. To validate this method, the stability of these two drugs was tested at the time of conservation of urine and plasma samples and during all steps of the analytical method.

Administration, Oral↗
PubMed1990

Doxorubicin and doxorubicinol: intra- and inter-individual variations of pharmacokinetic parameters.

Doxorubicin was given by short i.v. infusion (dose range 25-72 mg/m2) to 18 patients who underwent three to seven successive courses of chemotherapy (total, 57 courses). Plasma levels of doxorubicin and its major metabolite doxorubicinol were determined by high-performance liquid chromatography over a 48-h period after the infusion. Pharmacokinetic parameters for the parent drug and its metabolite were calculated for each course of treatment. The results show considerable inter- and intraindividual variations for most parameters. The coefficients of variation (CV) ranged from 37% to 93% (inter-individual) and from 6% to 59% (intra-individual). Nevertheless, we observed a good stability over successive courses for terminal half-life in six patients (CV, 6%-25%) and for clearance and AUC in four subjects (CV, 10%-22%). The ratio of the AUCs for doxorubicinol: doxorubicin averaged 0.514. The pharmacokinetic pattern of doxorubicinol was biphasic in plasma of the majority of patients. We propose a model for curve-fitting of these metabolite plasma concentrations that is based on two successive releases of the compound in the plasma compartment, separated by a lag time.

Adult↗
PubMed1989

Pharmacokinetics of sulpiride after intravenous administration in patients with impaired renal function.

Single intravenous doses of sulpiride 100 mg were administered to 18 patients with renal function impairment, and 6 healthy volunteers. The plasma concentration-time profile is described by a 2-compartment open model. The differences between the pharmacokinetic parameters of sulpiride for the 2 groups were statistically significant. Elimination half-life, mean residence time and area under the plasma concentration-time curve are significantly greater in renal failure; renal and total clearance, and the cumulative amount of unchanged sulpiride in urine, are significantly reduced but volume of distribution remains unchanged. Creatinine clearance was strongly correlated with renal clearance of sulpiride, elimination rate constant, area under the curve and cumulative amount excreted in urine. For patients with impaired or physiologically reduced renal function receiving long term sulpiride treatment, a 35 to 70% reduction in dose, or extension of the dosage interval by a factor of 1.5 to 3, may be required.

Adult↗
PubMed1989

[Prevention of cisplatin nephrotoxicity in cancer: adjusting the dosage with a computerized chrono-pump].

Platinum and its derivates are particularly efficient in treatment of ovarian and testis carcinomas. Nevertheless, the high nephrotoxicity of these drugs limits their use. It is known that nephrotoxicity appears when platinum plasmatic concentrations are higher than 1.5 mg/l. Moreover, the wide variability between patients and between cures, emphasizes the difficulties of utilization. Using a computerized pump and a program for individual dosage regimen, an efficient prevention of plasmatic overdosages have been realised and nephrotoxicity accidents have been avoided.

Aged↗
PubMed1985

[Determination of sulpiride and sultopride by high-performance liquid chromatography for pharmacokinetic studies].

A high-performance liquid chromatographic method with UV detection (226 nm) for the analysis of sulpiride and sultopride in body fluids has been developed. Plasma, red blood cell (RBC) and urine samples were extracted by chloroform at pH 10. Internal standards were a new substituted benzamide (N-[(ethyl-1-pyrrolidinyl-2)methyl] methoxy-2-ethylsulphonyl-5-benzamide, DAN) for the sulpiride assay and sulpiride for the sultopride assay. The detection limit in plasma and RBC was 10 ng/ml for sulpiride and 15 ng/ml for sultopride. The proposed techniques were selective, reliable and sensitive enough to be used for pharmacokinetic studies and drug monitoring. Some plasma and RBC data from pharmacokinetic studies in healthy volunteers (sulpiride) or patients (sultopride) are presented. Half-lives determined from either plasma or RBC concentrations were similar (7 h for sulpiride and 5 h for sultopride).

Amisulpride↗
PubMed1985

Quantitative thin-layer and high-performance liquid chromatographic determination of lorapride in biological fluids and a pharmacokinetic study in humans.

Lorapride has been determined in plasma, red blood cells, and urine by HPLC. The detection was performed at a short wavelength (226 nm), resulting in a detection limit of 10 ng/mL (amount injected was 3.5 ng). Reproducibility of analytical and chromatographic methods through statistical coefficients of variation was 4%. By TLC, only levels in urine were determined. Urine samples were spotted directly on the plate; lorapride was determined after spraying the plate with the Bratton-Marshall reagent, and measurements were carried out in the simultaneous reflectance and transmittance mode (540 nm). The detection limit was 10 ng spotted. Lorapride amounts in urine determined by the two methods were compared by statistical analysis. Examples of kinetics after intravenous and oral administration (100 mg) in humans are given.

Administration, Oral↗
PubMed1984

Sulpiride pharmacokinetics in humans after intramuscular administration at three dose levels.

Pharmacokinetics of the disinhibitory psychotropic agent sulpiride was investigated in 9 healthy male subjects after intramuscular administrations of 50, 100, and 200 mg in a 3 X 3 Latin square design. Plasma and urine concentrations were measured by HPLC for 36 and 48 h, respectively. The lowest detectable concentration was 10 ng/mL. Plasma concentration versus time and urinary excretion rate versus time curves were consistent with an open two-compartment body model, where mean +/- SD apparent half-lives of the absorption from muscle, lambda 1 distribution, and lambda 2 elimination phases were 6.96 +/- 2.64 min, 0.220 +/- 0.120 h, and 6.74 +/- 2.67 h, respectively. The initial volume of distribution was 0.145 +/- 0.063 L/kg, the steady-state volume of distribution was 0.639 +/- 0.184 L/kg, and the total clearance was 89.8 +/- 22.3 mL/min. The microscopic rate constants were k12 = 2.53 +/- 1.13 h-1, k21 = 0.674 +/- 0.197 h-1, and k10 = 0.635 +/- 0.298 h-1. Comparison of total clearance (89.8 mL/min), renal clearance (83.0 mL/min), and renal clearance of unbound drug (97.6 mL/min, f = 0.15) indicated that sulpiride is mainly excreted unchanged by the renal route, 93.1 +/- 6.6% of the administered dose being recovered unchanged in urine. Statistical evaluation of all the above parameters, determined at the three dosage levels, did not show any variations related to dose; the pharmacokinetics of sulpiride, over the dose range tested, was therefore linear and independent of dose. The two-compartment body model proposed was validated by digital computer simulation on a small digital computer (32K).

Adult↗